tbuckley/cabot-search huggingface dataset:
Durability of Heterologous and Homologous COVID-19 Vaccine Boosts
Authors: C. Sabrina Tan, Ai-ris Y. Collier, Jingyou Yu, Jinyan Liu, Abishek Chandrashekar, Katherine McMahan, Catherine Jacob-Dolan, Xuan He, Vicky Roy, Blake M. Hauser, Jennifer E. Munt, Michael L. Mallory, Melissa Mattocks, John M. Powers, Rita M. Meganck, Marjorie Rowe, Rachel Hemond, Esther A. Bondzie, Kate H. Jaegle, Ralph S. Baric, Aaron G. Schmidt, Galit Alter, Mathieu Le Gars, Jerald Sadoff, Dan H. Barouch
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting. <h3>Objective</h3> To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2. <h3>Design, Setting, and Participants</h3> In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022. <h3>Exposures</h3> Participants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2. <h3>Main Outcomes and Measures</h3> Humoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8<sup>+</sup>and CD4<sup>+</sup>T-cell responses were evaluated by intracellular cytokine staining assays. <h3>Results</h3> Among 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16. <h3>Conclusions and Relevance</h3> Heterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.
Association of atypical skin manifestations at the onset of systemic juvenile idiopathic arthritis with difficult-to-treat disease: A retrospective multicenter study
Authors: Laurye-Anne Eveillard, Pierre Quartier, Naim Ouldali, Brigitte Bader-Meunier, Florence Aeschlimann, Claire Abasq, Claire Ballot, Pauline Bouric, Alexandra Desdoits, Cécile Dumaine, Caroline Galeotti, Véronique Hentgen, Alain Lefevre-Utile, Aurélie Chausset, Thomas Hubiche, Ingrid Kupfer-Bessaguet, Stéphanie Leclerq-Mercier, Stéphanie Mallet, Isabelle Melki, Etienne Merlin, Juliette Miquel, Maryam Piram, Deborah Talmud, Nicolas Garcelon, Caroline Vinit, Anne Welfringer, Emmanuelle Bourrat, Ulrich Meinzer
Journal: Journal of the American Academy of Dermatology (2022)
Design and manufacture of a lyophilised faecal microbiota capsule formulation to GMP standards
Authors: Nur Masirah M. Zain, Daniëlle ter Linden, Andrew K. Lilley, Paul G. Royall, Sophia Tsoka, Kenneth D. Bruce, A. James Mason, Grace B. Hatton, Elizabeth Allen, Simon D. Goldenberg, Ben Forbes
Journal: Journal of Controlled Release (2022)

Faecal microbiota transplant (FMT) is an established and effective treatment for recurrent Clostridioides difficile infection (CDI) and has many other potential clinical applications. However, preparation and quality of FMT is poorly standardised and clinical studies are hampered by a lack of well-defined FMT formulations that meet regulatory standards for medicines. As an alternative to FMT suspensions for administration by nasojejunal tube or colonoscopy, which is invasive and disliked by many patients, this study aimed to develop a well-controlled, standardised method for manufacture of lyophilised FMT capsules and to provide stability data allowing storage for extended time periods. Faecal donations were collected from healthy, pre-screened individuals, homogenised, filtered and centrifuged to remove dietary matter. The suspension was centrifuged to pellet bacteria, which were resuspended with trehalose and lyophilised to produce a powder which was filled into 5 enteric-coated capsules (size 0). Live-dead bacterial cell quantitative PCR assay showed <10 fold viable bacterial load reduction through the manufacturing process. No significant loss of viable bacterial load was observed after storage at -80 °C for 36 weeks (p = 0.24, n = 5). Initial clinical experience demonstrated that the capsules produced clinical cure in patients with CDI with no adverse events reported (n = 7). We provide the first report of a detailed manufacturing protocol and specification for an encapsulated lyophilised formulation of FMT. As clinical trials into intestinal microbiota interventions proceed, it is important to use a well-controlled investigational medicinal product in the studies so that any beneficial results can be replicated in clinical practice.
Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance]
Authors: B. Saberzadeh-Ardestani, N.R. Foster, H.E. Lee, Q. Shi, S.R. Alberts, T.C. Smyrk, F.A. Sinicrope
Journal: Annals of Oncology (2022)
Hand-foot-and-mouth disease (HFMD) in children. Current scenario, and advancements in developing vaccines and therapeutics: An update – Correspondence
Authors: Sandip Chakraborty, Ranjan K. Mohapatra, Deepak Chandran, Rashmi Rana, Firzan Nainu, Chiranjib Chakraborty, Wanpen Chaicumpa, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ)
Authors: Ran Yan, Ruixue Jiang, Longwei Hu, Yuwei Deng, Jin Wen, Xinquan Jiang
Journal: International Journal of Oral Science (2022)

Abstract Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
A rapid decline in the anti–receptor-binding domain of the SARS-CoV-2 spike protein IgG titer in kidney transplant recipients after tixagevimab–cilgavimab administration
Authors: Ilies Benotmane, Aurélie Velay, Gabriela-Gautier Vargas, Jérôme Olagne, Noëlle Cognard, Françoise Heibel, Laura Braun-Parvez, Jonas Martzloff, Peggy Perrin, Romain Pszczolinski, Bruno Moulin, Samira Fafi-Kremer, Sophie Caillard
Journal: Kidney International (2022)
CHICAGO MEDICAL SOCIETY.
Journal: JAMA (1884)

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Clinicopathologic and proteomic characteristics of intratubular cytoplasmic AL amyloidosis
Authors: Vincent Javaugue, Alejandro Best Rocha, Samar M. Said, Dominick Santoriello, Jean Hou, Surendra Dasari, Jason D. Theis, Julie A. Vrana, Ibrahim Batal, Christopher Larsen, Glen S. Markowitz, Vivette D. D'Agati, Ellen D. McPhail, Nelson Leung, Samih H. Nasr
Journal: Kidney International (2022)
P-061: DE NOVO APPEARANCE OF VACUOLES IN TRANSFUSED RED BLOOD CELLS IN SICKLE CELL DISEASE PATIENTS WITH DEFECTIVE SPLENIC FUNCTION
Authors: DUMAS L., SISSOKO A., FRICOT A., SALAMA N., JOSEPH L., MANCEAU S., DOKMAK S., MICHEL A., MAITRE B., GACHET C., CAVAZZANA M., ROUSSEL C., BUFFET P.
Journal: HemaSphere (2022)

Purpose: Defective spleen function (hyposplenism) affects subjects with sickle cell disease (SCD) and is associated with complications. Red blood cell (RBC)-related markers are very accurate to assess spleen function. Vacuole-containing RBC (pocked RBC) are observed in high proportions (10 to 70%) of hyposplenic subjects whereas they do not exceed 5% of RBC in healthy subjects. Vacuoles in pocked RBC are considered by many as remnants of erythropoiesis-related processes. Materials and methods: Patients with SCD who benefit from an exchange transfusion program, have not only their own HbSS RBC but also transfused HbAA RBC in circulation. In vitro sickling “Emmel test” discriminates HbSS RBC, that sickle, from HbAA RBC, that do not. We perfused a mixture of HbSS RBC and HbAA RBC (from exchange transfusion left-overs) into human spleens ex-vivo. We then analyzed spleen sections and quantified vacuoles in RBC containing hemoglobin polymers or not. Results: Using Emmel test, we observed vacuoles in HbSS RBC but also in transfused HbAA RBC. Pocked HbAA RBC were more frequent in transfused SCD patients than in healthy subjects (25.1±4.41% vs. 2.8±2.1%). Into human spleen ex-vivo, we observed a high rate of vacuoles in either polymerized and non-polymerized RBC (29.8±3.7% vs. 17.9±5.8%). In our experimental set-up, HbAA RBC is deducted as the absence of polymerization. Conclusion: Taken together, these results strongly suggest that vacuoles are created de novo in transfused HbAA RBC.Counting vacuoles in RBC labeled with anti-HbS and anti-HbA antibody is ongoing to validate these observations. When the spleen is dysfunctional, these pocked RBC stay in circulation hence their validity as a spleen function marker. De novo appearance of vacuoles in transfused HbAA RBC likely impacts the kinetics of reappearance of pocked RBC in circulation following regular or exchange transfusion to hyposplenic subjects, and opens interesting prospects on cell processes involved in their genesis. M. CAVAZZANA declares a conflict of interest: Consultancy, Expert: consultant for Smart-Immune biotech
P-077: POTENTIAL BIOMARKERS IN THE PREVENTIVE DIAGNOSIS OF ACUTE COMPLICATIONS IN SICKLE CELL DISEASE
Authors: MOUMNI I., KHALFAOUI K., CHEBBI M., SAFRA I., MBARKA B., CHAOUACHI D., BEN KHALED M., OUEDERNI M., MELLOULI F., MENIF S.
Journal: HemaSphere (2022)

Purpose: Microparticles (MPs) are submicron vesicles derived from the plasma membrane of their parent cells. MPs have acquired a biological and clinical interest and are recognized as entities able to modulate many biological functions. Literature suggests that they may have a role in the pathophysiology and downstream manifestations of sickle cell disease (SCD). However, in SCD most of these MPs were derived by eryptosis, the programmed death of red blood cells. This present study aims to determine the cellular biomarkers to implement new and innovative methods of the preventive diagnosis of SCD acute complications. We propose to study the mechanisms involved in the triggering of eryptosis and to quantify microparticles derived from platelets, erythrocytes and endothelium of homozygous sickle cell patients. Materials and methods: Homozygous SCD patients and healthy donors were sampled for hematological and cellular assays. The exploration of eryptosis was performed by a flow cytometry by determining the viability parameters of red blood cells: the exposure of PS to the GR surface by annexin V labeling, the determination of intracellular calcium concentration by Fluo3-am labeling, quantification of ROS by CM-H2DCFDA labeling and determination of ceramides by specific labeling. The exploration of MPs was performed by evaluating the number of circulating microparticles as well as their cellular origin by triple labeling with Annexin V / Ac anti CD41 for platelets MPs/ Ac anti CD235a for erythrocytes MPs. Results: The outcome of our study indicated that Eryptosis in sickle cell patients is triggered essentially by high Ca2 + entry and narrowing of red blood cells. However, the pathway of ceramides and ERO can also considered a stimulating factor of eryptosis. Eryptosis ensures healthy erythrocyte quantity in circulation whereas excessive eryptosis is the cause of acute anemia and may contribute to vaso-occlusive crisis in sickle cell patients. For MPs study, we confirmed that microparticles derived from platelets and erythrocytes clearly increased in SCD patients, with predominance of the number of erythrocyte microparticles. This suggests that erythrocytes MPs may contribute to thrombotic risk in sickle cell patients. Conclusion: Our research describes promising biomarkers of the preventive diagnosis of acute complication in sickle cell disease. These findings allow considering the eryptosis and circulating MPs as potential biomarkers for implementation a new preventive diagnosis method. The authors do not declare any conflict of interest
P-033: CLINICAL AND HEMATOLOGICAL FOLLOW UP OF SICKLE CELL DISEASE PATIENTS IN A REMOTE CITY IN A COUNTRY WITH LIMITED RESOURCES
Authors: MBIYA-MUKINAYI B., KALOMBO-KALENDA D., MUKENDI-NKESU Y., DAUBIE V., KALENDA-MPOYI J., BIBOYI-MUKENDI P., DISASHI-TUMBA G., GULBIS B.
Journal: HemaSphere (2022)

Purpose: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. While reference sickle cell centers have been implemented in capital cities of African countries and have proven to be beneficial for SCD patients. In the Democratic Republic of Congo, they have never been set up in remote areas for families with low or very low sources of income. Materials and methods: A cohort of 143 children with SCD aged 10 years old (IQR (interquartile range): 6–15 years) (sex ratio male/female = 1.3) were clinically followed for 12 months without any specific intervention aside from the management of acute events, and then for 12 months with a monthly medical visit, biological follow-up, and chemoprophylaxis (folic acid/penicillin), adequate fluids and malaria prevention. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). The implementation of standardized and regular follow-ups in a new sickle cell reference center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease in the lymphocyte count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. Conclusion: The creation of a sickle cell reference center and the regular follow-up of children with sickle cell disease are possible and applicable in the context of a remote city of an African country, and represent simple and accessible measures that can reduce the morbimortality of children with sickle cell disease.The city of Mbujimayi in the Democratic Republic of the Congo The authors do not declare any conflict of interest
Cardiovascular Effects of Home Dialysis Therapies: A Scientific Statement From the American Heart Association
Authors: Mark J. Sarnak, Bourne L. Auguste, Edwina Brown, Alexander R. Chang, Glenn M. Chertow, Mary Hannan, Charles A. Herzog, Annie-Claire Nadeau-Fredette, Wai Hong Wilson Tang, Angela Yee-Moon Wang, Daniel E. Weiner, Christopher T. Chan
Journal: Circulation (2022)

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Currently, thrice-weekly in-center hemodialysis for 3 to 5 hours per session is the most common therapy worldwide for patients with treated kidney failure. Outcomes with thrice-weekly in-center hemodialysis are poor. Emerging evidence supports the overarching hypothesis that a more physiological approach to administering dialysis therapy, including in the home through home hemodialysis or peritoneal dialysis, may lead to improvement in several cardiovascular risk factors and cardiovascular outcomes compared with thrice-weekly in-center hemodialysis. The Advancing American Kidney Health Initiative, which has a goal of increasing the use of home dialysis, is aligned with the American Heart Association’s 2024 mission to champion a full and healthy life and health equity. We conclude that incorporation of interdisciplinary care models to increase the use of home dialysis therapies in an equitable manner will contribute to the ultimate goal of improving outcomes for patients with kidney failure and cardiovascular disease.
P-084: INFECTIOUS PROFILE OF SICKLE CELL PATIENTS IN THE HEMATOLOGY DEPARTMENTS OF CONAKRY UNIVERSITY HOSPITAL
Authors: DIAKITE M., KANTE A., TOFOITA BINTY A., CAMARA F., SAKO F.
Journal: HemaSphere (2022)

Purpose: Infection a factor triggering sickle cell crises, a frequent cause of hospitalization as well as a factor of poor prognosis in sickle cell patients. The objective is to contribute to improving the management of sickle cell disease in Guinea by determining their infectious profile. Materials and methods: This was a descriptive and analytical prospective study lasting 08 months from September 01 to April 30, 2021 carried out at the University Hospital of Conakry. We included in this study all patients hospitalized for sickle cell disease in our departments with an infectious syndrome, who had carried out the infectious assessment. Results: out of 68 sickle cell patients included, 62 had an infection, i.e. 91.17%, mean patient age was 26.17±11.97 years,the female sex wasslightlyrepresented i.e. 51.61%,and a female to male sex ratio of 1.06. The most common reasons for consultation were osteo-articular pain 96.77% followed by fever 95.16%. The most common type of infection in our study was parasitic 93.55%, followed by bacterial 30.65%. The germs found were: Escherichia coli (68.75%), Salmonella typhi (31.25%), staphylococcus (50.00%), Koch bacillus 0.14%, candida albicans (66.66%) Plasmodium (87.10 %), Ascaris Eggs (46.15%), Amoeba Cyst (23.07%), Hookworm (11.54%), HBV (7.01%), HIV (5.26%), Taénia (7.69%), Gardenerella vaginalis (33.33%) and Neisseria Gonorhée (25.00%). The management of infections was made according to the etiology found: antiparasitics (Artesunate, Artemether/Lumefantrine, Albendazole, praziquantel), antibiotics (Ceftriaxone‚ metronidazole, amoxicillin-clavulanic acid, ciprofloxacin), antifungals (Nystatin, Fluconazole, Miconazole and antiretrovirals (Emtricitabine, Lamuvidine and Tenofovir).evolution after treatment was favorable in88.71% of cases and we noted 4.48% transfer, 3.23% discharge against medical advice and 3.23% death. Conclusion: Infection is a common cause of hospitalization in sickle cell patients. Bone and joint pain and Fever were the most frequent clinical presentations, the types of infections were bacterial, parasitic, viral and fungal. The treatment of infections was made of antibacterials, antiparasitics, antivirals and antifungals. The authors do not declare any conflict of interest
P-081: EVALUATION OF THE SEXUALITY OF ADULT HOMOZYGOUS SICKLE CELL PATIENTS WITH A HISTORY OF PRIAPISM IN SENEGAL
Authors: SECK M., GAYE O., GUÈYE S., TOURÉ S., KEITA M., DIALLO A., BOUSSO E., FAYE B., DIOP S.
Journal: HemaSphere (2022)

Purpose: Priapism is a frequent vaso-occlusive complication of sickle cell disease, the major risk of which is the impairment of erectile function. The objective of this study was to evaluate the sexuality of SS sickle cell patients with a history of priapism. Materials and methods: This was a case-control study of adult SS sickle cell patients. The occurrence of priapism and the nature of the priapism were investigated. Patients were divided into three groups: Group 1 (no priapism), Group 2 (intermittent priapism) and Group 3 (acute priapism). The sexuality of the patients was studied using the IIEF-15 questionnaire. The scores were compared between the three groups to look for an impact of priapism on their sexual life. Results: We interviewed 191 SS sickle cell patients. The mean age was 27.1 +/- 7.1 years. Priapism was observed in 43.5%. Only 77 patients were eligible for the IIEF15 questionnaire. Groups 1 and 2 had significantly better results than group 3 on EF and FO scores. There was no significant difference in EF and FO scores between groups 1 and 2. There was no significant difference between the three groups for SD, IS, OS scores. The impairment of erectile function in group 2 was related to the age of the first and last episode of priapism. The impairment of erectile function in group 3 was related to the duration of evolution. Conclusion: This study shows that acute or intermittent priapism is responsible for impaired erectile function in adult SS sickle cell patients. Associated prognostic factors were prolonged duration of priapism, age of first and last episode of priapism. The authors do not declare any conflict of interest